The Link Between RA and ‘Brain Fog’

Could there be a link between always losing your keys and rheumatoid arthritis? Perhaps, researchers say.

By Timothy Gower

As you know, rheumatoid arthritis is a disease of the joints, but some people with RA say that it can also take a toll on a very important organ: the brain. They describe feeling forgetful, unable to concentrate and gripped by the “blahs.” In other words, they say that RA gives them an unshakable case of brain fog.

Brain fog isn’t a medical term, but doctors have long recognized that patients with certain physical conditions (such as lupus and multiple sclerosis) can experience cognitive dysfunction, or the diminished ability to think, learn, remember and perform other mental tasks. Not all doctors who treat RA are convinced that brain fog represents an important concern for their patients. Yet recent research offers clues that diseases featuring chronically elevated inflammation, such as RA, may hinder healthy brain performance.

“I see it all the time,” says Marian Rissenberg, PhD, a neuropsychologist who works with patients coping with cognitive problems at Northern Westchester Hospital in Mount Kisco, New York. “These people are not malingerers.”

Surprisingly Common

No one is sure how many people with RA experience brain fog, but a few researchers have tried to get a handle on the question by administering standardized cognitive tests to patients. A pair of small studies performed in 2002 and 2004 found that anywhere from 30 percent to 71 percent of RA patients performed poorly on various cognitive tests.

More recently, a team at the University of California at San Francisco conducted one of the largest investigations on the cognitive abilities of RA patients to date, which was published in Arthritis Care & Research in August 2012. Researcher So Young Shin and her colleagues gave a wide-ranging battery of cognitive tests to 115 RA patients. Shin’s group found that many of the study participants struggled with mental clarity and sharpness: 31 percent scored poorly on four or more of 16 different measurements of cognitive ability.

Who Gets Brain Fog — and Why?

What is it about RA that might cloud the mind and dulls the wits? “At this point, we can only assume that several mechanisms… may affect cognitive impairment in RA,” says Shin via e-mail. Shin’s study found that patients who used corticosteroid drugs — a common treatment for RA — and who had risk factors for heart disease (such as high blood pressure and high cholesterol) were most likely to have cognitive dysfunction. She notes that past studies have these medications and heart risk factors to fuzzy thinking, too, though no one is sure why.

What’s more, some studies suggest that the depression and anxiety that can accompany coping with chronic pain may impair cognition. A 2010 experiment at the University of Windsor in Ontario, Canada, found that RA patients with high levels of pain did poorly on tests of so-called executive functions, which include planning, decision-making, and working memory (which helps you to follow instructions, among other roles).

As you know, rheumatoid arthritis is a disease of the joints, but some people with RA say that it can also take a toll on a very important organ: the brain. They describe feeling forgetful, unable to concentrate and gripped by the “blahs.” In other words, they say that RA gives them an unshakable case of brain fog.

Brain fog isn’t a medical term, but doctors have long recognized that patients with certain physical conditions (such as lupus and multiple sclerosis) can experience cognitive dysfunction, or the diminished ability to think, learn, remember and perform other mental tasks. Not all doctors who treat RA are convinced that brain fog represents an important concern for their patients. Yet recent research offers clues that diseases featuring chronically elevated inflammation, such as RA, may hinder healthy brain performance.

“I see it all the time,” says Marian Rissenberg, PhD, a neuropsychologist who works with patients coping with cognitive problems at Northern Westchester Hospital in Mount Kisco, New York. “These people are not malingerers.”

Surprisingly Common

No one is sure how many people with RA experience brain fog, but a few researchers have tried to get a handle on the question by administering standardized cognitive tests to patients. A pair of small studies performed in 2002 and 2004 found that anywhere from 30 percent to 71 percent of RA patients performed poorly on various cognitive tests.

More recently, a team at the University of California at San Francisco conducted one of the largest investigations on the cognitive abilities of RA patients to date, which was published in Arthritis Care & Research in August 2012. Researcher So Young Shin and her colleagues gave a wide-ranging battery of cognitive tests to 115 RA patients. Shin’s group found that many of the study participants struggled with mental clarity and sharpness: 31 percent scored poorly on four or more of 16 different measurements of cognitive ability.

Who Gets Brain Fog — and Why?

What is it about RA that might cloud the mind and dulls the wits? “At this point, we can only assume that several mechanisms… may affect cognitive impairment in RA,” says Shin via e-mail. Shin’s study found that patients who used corticosteroid drugs — a common treatment for RA — and who had risk factors for heart disease (such as high blood pressure and high cholesterol) were most likely to have cognitive dysfunction. She notes that past studies have these medications and heart risk factors to fuzzy thinking, too, though no one is sure why.

What’s more, some studies suggest that the depression and anxiety that can accompany coping with chronic pain may impair cognition. A 2010 experiment at the University of Windsor in Ontario, Canada, found that RA patients with high levels of pain did poorly on tests of so-called executive functions, which include planning, decision-making, and working memory (which helps you to follow instructions, among other roles).

A 2009 study by University of Calgary researcher Mark Swain, MD, and colleagues offers a potential explanation for why inflammation in distant parts of the body may induce brain fog. By studying lab mice, Swain and his team found that inflamed body tissues (in this case, inflamed livers) transmit signals to the brain that can produce symptoms such as malaise and fatigue. Swain explains that chronic inflammation can “activate” immune cells in the bloodstream, causing them to enter the brain and release proteins called cytokines. Normally, these proteins help regulate how your immune system responds to threats such as infections. But inside the brain, cytokines may alter the quantity and activity of critical chemical messengers known as neurotransmitters. “When you alter neurotransmitter systems, you can change behavior, emotion, your desire to get up and go,” says Dr. Swain.

Clearing the Fog

Unruly cytokines cause more than brain fog, of course. Cytokines such as tumor necrosis factor (TNF) and interleukin-6 (IL-6) promote joint inflammation, which is why newer RA drugs known as biologic agents were designed to block them. Interestingly, RA patients who had previously complained of fatigue and mental lethargy often say they feel like their old selves soon after they start receiving TNF inhibitors (such as etanercept or adalimumab) or other biologic agents — even before their joint pain improves.

“It can be within an hours of receiving treatment,” says Dr. Swain. In fact, last year a preliminary study in the United Kingdom found an improvement on IQ test scores among 15 RA patients given adalimumab.

Getting pain and stiffness of RA under control also helps patients sleep better, which has the ripple effect of making people feel sharper, points out rheumatologist David Borenstein, MD, a clinical professor of medicine at George Washington University Medical Center in Washington, D.C.

“Patients will say ‘I have trouble thinking because I’m so tired,’” notes Dr. Borenstein. But adding a biologic agent to their regimen helps them get more restorative shut-eye. “Suddenly they’re saying, ‘I don’t need to take a nap in the afternoon anymore. I feel energized.’”

Dr. Borenstein says it’s also important for RA patients who feel foggy-brained to improve their sleep habits by taking steps such as limiting caffeine consumption to the morning and not exercising close to bed time. But do get plenty of physical activity, he advises, which causes the body to generate endorphins and other mood-boosting hormones. “They make you feel better,” says Dr. Borenstein.

Rissenberg says that people with illness-related cognitive problems can offset the effects of brain fog with certain strategies, such as using a day planner and sticking to routines to help overcome forgetfulness or lack of motivation. Some people find that they’re more clear-headed at certain times of the day; reserve those periods for tasks requiring you to stay focused and alert.